title: When are cellular oscillators sufficient for sequential segmentation?
abstract: Sequential segmentation during embryogenesis involves the generation of a repeated pattern along the embryo, which is concurrently undergoing axial elongation by cell division. Most mathematical models of sequential segmentation involve inherent cellular oscillators, acting as a segmentation clock. The cellular oscillation is assumed to be governed by the cell's physiological age or by its interaction with an external morphogen gradient. Here, we address the issue of when cellular oscillators alone are sufficient for predicting segmentation, and when a morphogen gradient is required. The key to resolving this issue lies in how cells determine positional information in the model--this is directly related to the distribution of cell divisions responsible for axial elongation. Mathematical models demonstrate that if axial elongation occurs through cell divisions restricted to the posterior end of the unsegmented region, a cell can obtain its positional information from its physiological age, and therefore cellular oscillators will suffice. Alternatively, if axial elongation occurs through cell divisions distributed throughout the unsegmented region, then positional information can be obtained through another mechanism, such as a morphogen gradient. Two alternative ways to establish a morphogen gradient in tissue with distributed cell divisions are presented--one with diffusion and the other without diffusion. Our model produces segment polarity and a distribution of segment size from the anterior-to-posterior ends, as observed in some systems. Furthermore, the model predicts segment deletions when there is an interruption in cell division, just as seen in heat shock experiments, as well as the growth and final shrinkage of the presomitic mesoderm during somitogenesis.
authors.affiliation: Department of Mathematics and Statistics, University of Melbourne, Victoria 3010, Australia.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Chisholm
authors.forename: Barry D
authors.initials: BD
authors.lastname: Hughes
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Landman
authors.forename: Georg
authors.initials: G
authors.lastname: Mayer
authors.forename: Paul M
authors.initials: PM
authors.lastname: Whitington
mesh_terms: D001683:Biological Clocks / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D002455:Cell Division; D016764:Cell Polarity; D002477:Cells / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D047108:Embryonic Development; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D008954:Models, Biological; D019170:Somites / Q000166:cytology / Q000196:embryology